Copolymers of absorbable polyoxaesters

ABSTRACT

The present invention describes a polyoxaester copolymer and blends thereof that may be used to produce hydrogels, surgical devices such as sutures, sutures with attached needles, molded devices, drug matrices, adhesives, sealants and the like. The invention also contemplates a process for producing these polyesters. The polyoxaester copolymers of the present invention are formed from a first divalent repeating unit of formula IA: 
     
       
         [—O—C(O)—R 30 —C(O)—]  IA  
       
     
     a second divalent repeating unit of the formula IB: 
     
       
         [O—C(O)—C(R 1 )(R 2 )—O—R 3 —O—C(R′ 1 )(R′ 2 )—C(O)—]  IB  
       
     
     and a third repeating unit selected from the group of formulas consisting of: 
     
       
         [—O—R 4 —] A ,  II  
       
     
     
       
         [—O—R 5 —C(O)—] B ,  III  
       
     
     
       
         ([—O—R 5 —C(O)] P —O—) L G  XI  
       
     
     and combinations thereof. These aliphatic polyoxaesters may be blended with other polymers that are preferably biocompatable.

This patent is a continuation of U.S. patent application Ser. No.09/062,881, filed on Apr. 20, 1998, now U.S. Pat. No. 6,147,168 which isa continuation-in-part of U.S. patent application Ser. No. 08/964,733,filed on Nov. 5, 1997, now U.S. Pat. No. 5,859,150, which is acontinuation-in-part of Ser. No. 08/744,289, filed on Nov. 6, 1996, nowU.S. Pat. No. 5,698,213, which is a continuation-in-part of Ser. No.08/611,119, filed Mar. 5, 1996, now U.S. Pat. No. 5,607,687, which is acontinuation-in-part of Ser. No. 08/554,011, filed Nov. 6, 1995, nowabandoned, which is a continuation-in-part of Ser. No. 08/399,308, filedMar. 6, 1995, now U.S. Pat. No. 5,464,929 all assigned to Ethicon, Inc.

FIELD OF THE INVENTION

The present invention relates to a bioabsorbable copolymeric materialand blends thereof and more particularly to absorbable surgical productsmade from such copolymers and blends thereof.

BACKGROUND OF THE INVENTION

Since Carothers early work in the 1920s and 1930s, aromatic polyestersparticularly poly(ethylene terephthalate) have become the mostcommercial important polyesters. The usefulness of these polymers isintimately linked to the stiffening action of the p-phenylene group inthe polymer chain. The presence of the p-phenylene group in the backboneof the polymer chain leads to high melting points and good mechanicalproperties especially for fibers, films and some molded products. Infact poly(ethylene terephthalate) has become the polymer of choice formany common consumer products, such as one and two liter soft drinkcontainers.

Several related polyester resins have been described in U.S. Pat. Nos.4,440,922, 4,552,948 and 4,963,641 which seek to improve upon theproperties of poly(ethylene terephthalate) by replacing terephthalicacid with other related dicarboxylic acids which contain phenylenegroups. These polymers are generally designed to reduce the gaspermeability of aromatic polyesters.

Other aromatic polyesters have also been developed for specialtyapplications such as radiation stable bioabsorbable materials. U.S. Pat.Nos. 4,510,295, 4,546,152 and 4,689,424 describe radiation sterilizablearomatic polyesters which can be used to make sutures and the like.These polymers like, poly(ethylene terephthalate), have phenylene groupsin the backbone of the polymers.

However, less research has been reported on aliphatic polyesters. AfterCarothers initial work on polyesters, aliphatic polyesters weregenerally ignored because it was believed that these materials had lowmelting points and high solubilities. The only aliphatic polyesters thathave been extensively studied are polylactones such as polylactide,polyglycolide, poly(p-dioxanone) and polycaprolactone. These aliphaticpolylactones have been used primarily for bioabsorbable surgical suturesand surgical devices such as staples. Although polylactones have provento be useful in many applications they do not meet all the needs of themedical community. For example films of polylactones do not readilytransmit water vapor, therefore, are not ideally suited for use asbandages where the transmission of water vapor would be desired.

Recently there has been renewed interest in non-lactone aliphaticpolyesters. U.S. Pat. No. 5,349,028 describes the formation of verysimple aliphatic polyesters based on the reaction of a diol with adicarboxylic acid to form prepolymer chains that are then coupledtogether. These polyesters are being promoted for use in fibers andmolded articles because these polyesters are biodegradable after theyare buried such as in a landfill. However, these materials are notdisclosed as being suitable for use in surgical devices.

To address the deficiencies in the polymers described in the prior artwe invented a new class of polymers which are disclosed in U.S. Pat.Nos. 5,464,929; 5,595,751; 5,597,579; 5,607,687; 5,618,552; 5,620,698;5,645,850; 5,648,088; 5,698,213; and 5,700,583 (all of which are herebyincorporated by reference). This new class of polymers is hydrolyzableand suitable for a variety of uses including medical applications. Tofurther broaden the possible uses for these polymers we are disclosingand claiming herein copolymers of the polyoxaamides (which includespolyoxaesteramides) and blends thereof with other polymers with modifiedhydrolysis profiles. These polymers may be used in industrial andconsumer applications where biodegradable polymers are desirable, aswell as, in medical devices.

SUMMARY OF THE INVENTION

We have discovered a new class of synthetic copolymeric materials andblends thereof that may be used to produce surgical devices such asmolded devices, drug delivery matrices, coatings, lubricants and thelike. The invention also contemplates a process for producing thecopolymers and blends. The copolymers and blends of the presentinvention comprise a polyoxaester copolymer having a first divalentrepeating unit of formula IA:

[—O—C(O)—R₃₀—C(O)—]  IA

a second divalent repeating unit of the formula IB:

[—O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IB

and a third repeating unit selected from the group of formulasconsisting of:

[—O—R₄—]_(A),  II

[—O—R₅—C(O)]_(B),  III

([—O—R₅—C(O)]_(P)—O—)_(L)G  XI

and combinations thereof, wherein R₃₀ is an alkylene, arylene,arylalkylene, substituted alkylene, substituted arylene and substitutedalkylarylene provided that R₃₀ cannot be—[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)₁₋₂—; R₁, R′₁, R₂ and R′₂ areindependently hydrogen or an alkyl group containing 1 to 8 carbon atoms;R₃ is an alkylene unit containing from 2 to 12 carbon atoms or is anoxyalkylene group of the following formula:

—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IV

wherein C is an integer in the range of from 2 to about 5, D is aninteger in the range of from about 0 to about 2,000, and E is an integerin the range of from about 2 to about 5, except when D is zero, in whichcase E will be an integer from 2 to 12; R₄ is an alkylene unitcontaining from 2 to 8 carbon atoms; A is an integer in the range offrom 1 to 2,000; R₅ is selected from the group consisting of—C(R₆)—(R₇)—, —(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—, —(CH₂)₅—,—(CH₂)_(F)—O—C(O)— and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ are independentlyhydrogen or an alkyl containing from 1 to 8 carbon atoms; R₈ is hydrogenor methyl; F is an integer in the range of from 2 to 6; B is an integerin the range of from 1 to n such that the number average molecularweight of formula III is less than about 200,000, preferably less thanabout 100,000 and most preferably less than 40,000; P is an integer inthe range of from 1 to m such that the number average molecular weightof formula XI is less than about 1,000,000, preferably less than about200,000 and most preferably less than 40,000; G represents the residueminus from 1 to L hydrogen atoms from the hydroxyl group of an alcoholpreviously containing from 1 to about 200 hydroxyl groups; and L is aninteger from about 1 to about 200.

Additionally, the present invention describes devices, coatings, drugrelease matrices, adhesives, sealants and prepolymers.

DETAILED DESCRIPTION OF THE INVENTION

The aliphatic polyoxaesters of the present invention are the reactionproduct of 1) a dicarboxylic acid; 2) an aliphatic polyoxycarboxylicacid; and 3) at least one of the following compounds: a diol (orpolydiol), a lactone (or lactone oligomer), a coupling agent orcombination thereof. For the purpose of this application aliphatic shallmean an organic compound having a straight, branched, or cyclicarrangement of carbon atoms (i.e. alkanes, olefins, cycloalkanes,cycloolefins and alkynes).

Suitable non-dioxycarboxylic acids may be polyfunctional for use in thepresent invention generally have the following formula:

HOOC—R₃₀—COOH  VA

wherein R₃₀ is an alkylene, arylene, arylalkylene, substituted alkylene,substituted arylene and substituted alkylarylene provided that R₃₀cannot be [—C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; and thesenon-dioxycarboxylic acids may be substituted with heteroatoms or groups.The non-dioxycarboxylic acids of the present invention are generallypolycarboxylic acids and more preferably dicarboxylic acids. However,monocarboxylic acids may be used as end caps for the copolymer that areformed. If carboxylic acids are used that have more than two carboxylicacid groups the resulting copolymers may form star shapes or crosslinkedmatrices depending on the concentration of the carboxylic acids havingmore than two carboxylic acid groups. Representative unsaturatedaliphatic dicarboxylic acids include, but are not limited to, thoseselected from the group consisting of maleic acid, fumaric acid andcombinations thereof. Representative saturated aliphatic dicarboxylicacids include, but are not limited to, those selected from the groupconsisting of oxalic acid, malonic acid (propanedioic), succinic(butanedioic), glutaric (pentanedioic), adipic (hexadioic), pimelic(heptanedioic), octanedioic, nonanedioic, decanedoic, undecanedioic,dodecanedioic, hendecanedioic, tetradecanedioic, pentadecanedioic,hexadecanedioic, heptadecandioic, octadecanedioic, nonadecanedioic,eicosanedioic acid and combinations thereof. Representative aromaticdicarboxylic acids include, but are not limited to, those selected fromthe group consisting of phthalic acid, isophthalic acid, terephthalicacid, phenylenediglycolic acid, caboxymethoxybenzoic acid andcombinations thereof.

Suitable aliphatic alpha-oxycarboxylic acids for use in the presentinvention generally have the following formula:

HO—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—OH  V

wherein R₁, R′₁, R₂ and R′₂ are independently selected from the groupconsisting of hydrogen or an alkyl group containing from 1 to 8 carbonatoms and R₃ is an alkylene containing from 2 to 12 carbon atoms or isan oxyalkylene group of the following formula:

—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IV

wherein C is an integer in the range of from about 2 to about 5, D is aninteger in the range of from about 0 to about 2,000 and preferably from0 to 12, and E is an integer in the range of from about 2 to about 5.These aliphatic alpha-hydroxycarboxylic acids may be formed by reactinga diol or polydiol with an alpha-halocarboxylic acid such bromoaceticacid or chloroacetic acid under suitable conditions.

Suitable diols or polydiols for use in the present invention are diol ordiol repeating units with up to 8 carbon atoms having the formula:

H[—(O—R₄—)_(A)]OH  VI

wherein R is an alkylene unit containing from 2 to 8 methylene units; Ais an integer in the range of from 1 to about 2,000 and preferably from1 to about 1000. Examples of suitable diols include diols selected fromthe group consisting of 1,2-ethanediol (ethylene glycol),1,2-propanediol (propylene glycol), 1,3-propanediol, 1,4-butanediol,1,5-pentanediol, 1,3-cyclopentanediol, 1,6-hexanediol,1,4-cyclohexanediol, 1,8-octanediol and combinations thereof. Examplesof preferred polydiols include polydiols selected from the groupconsisting of polyethylene glycol (H[—O—CH₂—CH₂—]_(A)OH) andpolypropylene glycol (H[—O—CH₂—CH(CH₃)—]_(A)OH).

The ratio of non-dioxycarboxylic acid to aliphatic oxydicarboxylic acidshould be in the range of from about 1:99 to about 99:1. The rate ofhydrolysis can be controlled, in part, by changing the ratio of thenon-oxadiacid-based moeties to those of the oxadiacid-based moeties. Asthe concentration of the non-oxadiacid-based moeties increases, thehydrolysis rate will be lower. Besides taking into account thehydrophilic/hydrophobic nature of the reactants, one can also exertcontrol through the steric nature of the alcohol, amine, and aminoalcohol groups employed. Thus the hydrolysis rate of an ester based on asecondary alcohol is slower than that of an ester based on a primaryalcohol group. The relative concentration of aromatic moieties willeffect the hydroylsis rate. Additionally, the presence of aromaticmoieties will help resist the loss of properties that may occur duringsterilization by gamma irradiation. Higher concentrations of such groupswill be better for cobalt sterilizable products.

The copolymer produced by reacting the non-dioxydicarboxylic acid andaliphatic dioxycarboxylic acid with the diols discussed above shouldprovide a copolymer generally having the formula:

[O—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—]_(N′)[—O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—]_(N)  VII

wherein R₁, R₂, R′₁, R′₂, R₃, R₄ and A are as described above; R′₄ andA′ have the same definitions respectively as R₄ and A but varyindependently therefrom; N and N′ are integers in the range of fromabout 1 to about 10,000 and preferably is in the range of from about 10to about 1,000 and most preferably in the range of from about 50 toabout 200.

Suitable lactone monomers that may be used in the present inventiongenerally have the formula:

These lactone monomers may be polymerized to provide copolymers of thefollowing general structures:

H[—O—R₅—C(O)—]_(B)OH  IX

(H[—O—R₅—C(O)]_(P)—O—)_(L)G  X

wherein R₅ is selected from the group consisting of —C(R₆)(R₇)—,—(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—, —(CH₂)₅—, —(CH₂)_(F)—O—C(O)—and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ are independently hydrogen or analkyl containing from 1 to 8 carbon atoms; Re is hydrogen or methyl; Fis an integer of from about 2 to 6; B is an integer in the range of from1 to n such that the number average molecular weight of formula IX isless than about 200,000, preferably less than 100,000, and mostpreferably less than 40,000; P is an integer in the range of from 1 to msuch that the number average molecular weight of formula X is less than1,000,000 about, preferably less than about 200,000 and most preferablyless than 40,000; G represents the residue minus from 1 to L hydrogenatoms from the hydroxyl groups of an alcohol previously containing from1 to about 200 hydroxyl groups; and L is an integer from about 1 toabout 200. In one embodiment G will be the residue of a dihydroxyalcohol minus both hydroxyl groups. In another embodiment of the presentinvention G may be a polymer containing pendent hydroxyl groups(including polysaccharides). Suitable lactone-derived repeating unitsmay be generated from the following monomers include but are not limitedto lactone monomers selected from the group consisting of glycolide,d-lactide, 1-lactide, meso-lactide, ε-caprolactone, p-dioxanone,trimethylene carbonate, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one andcombinations thereof.

The copolymer formed by reacting the above described diol (or polydiol)VI, the nonoxydicarboxylic acids and aliphatic polyoxycarboxylic acid Vmay also be copolymerized in a condensation polymerization with thelactone polymers IX described above to form a polymer generally of theformula:

[(—C(O)—R₃₀—C(O)—(O—R′₄)′_(A)—O)′_(S)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)(C(O)—R₅—O)_(B)]_(W)  XII

 or

[(—C(O)—R₃₀—C(O)—(O—R′₄)′_(A)—O)′_(S)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)([—O—R₅—C(O)]_(P)—O—)_(L)G]_(W)  XIII

wherein S and S′ are integers in the range of from about 1 to about10,000 and preferably from about 1 to about 1,000 and W is an integer inthe range of from about 1 to about 1,000. These copolymers may be madein the form of random copolymers or block copolymers. To the diols,nonoxydicarboxylic acids, aliphatic polyoxycarboxylic acids and lactonemonomers described above there may be added a coupling agent selectedfrom the group consisting of polyfunctional (i.e. trifunctional ortetrafunctional) polyols, oxycarboxylic acids, and polybasic carboxylicacids (or acid anhydrides thereof). The addition of the coupling agentscauses the branching of long chains, which can impart desirableproperties in the molten state to the polyester prepolymer. Examples ofsuitable polyfunctional coupling agents include trimethylol propane,glycerin, pentaerythritol, malic acid, citric acid, tartaric acid,trimesic acid, propane tricarboxylic acid, cyclopentane tetracarboxylicanhydride and combinations thereof.

The amount of coupling agent to be added before gelation occurs is afunction of the type of coupling agent used and the polymerizationconditions of the polyoxaester or molecular weight of the prepolymer towhich it is added. Generally in the range of from about 0.1 to about 10mole percent of a trifunctional or a tetrafunctional coupling agent maybe added based on the moles of polyoxaester copolymers present oranticipated from the synthesis.

The polymerization of the polyoxaester copolymer is preferably performedunder melt polycondensation conditions in the presence of anorganometallic catalyst at elevated temperatures. The organometalliccatalyst is preferably a tin-based catalyst e.g. stannous octoate. Thecatalyst will preferably be present in the mixture at a mole ratio ofdiol, nonoxycarboxylic acid, aliphatic polyoxycarboxylic acid andoptionally lactone monomer to catalyst will be in the range of fromabout 15,000 to 80,000/1. The reaction is preferably performed at atemperature no less than about 120° C. under reduced pressure. Higherpolymerization temperatures may lead to further increases in themolecular weight of the copolymer, which may be desirable for numerousapplications. The exact reaction conditions chosen will depend onnumerous factors, including the properties of the copolymer desired, theviscosity of the reaction mixture, and the glass transition temperatureand softening temperature of the polymer. The preferred reactionconditions of temperature, time and pressure can be readily determinedby assessing these and other factors.

Generally, the reaction mixture will be maintained at about 220° C. Thepolymerization reaction can be allowed to proceed at this temperatureuntil the desired molecular weight and percent conversion is achievedfor the copolymer, which will typically take about 15 minutes to 24hours. Increasing the reaction temperature generally decreases thereaction time needed to achieve a particular molecular weight.

In another embodiment, copolymers of polyoxaester can be prepared byforming a polyoxaester prepolymer polymerized under meltpolycondensation conditions, then adding at least one lactone monomer orlactone prepolymer. The mixture would then be subjected to the desiredconditions of temperature and time to copolymerize the prepolymer withthe lactone monomers.

The molecular weight of the prepolymer as well as its composition can bevaried depending on the desired characteristic, which the prepolymer isto impart to the copolymer. However, it is preferred that thepolyoxaester prepolymers from which the copolymer is prepared have amolecular weight that provides an inherent viscosity between about 0.2to about 2.0 deciliters per gram (dl/g) as measured in a 0.1 g/dlsolution of hexafluoroisopropanol at 25° C. Those skilled in the artwill recognize that the polyoxaester prepolymers described herein canalso be made from mixtures of more than one diol or dioxycarboxylicacid.

One of the beneficial properties of the polyoxaester made by the processof this invention is that the ester linkages are hydrolyticallyunstable, and therefore the copolymer is bioabsorbable because itreadily breaks down into small segments when exposed to moist bodilytissue. By controlling the ratio of oxycarboxylic acid tononoxycarboxylic acid the hydrolysis rate of the resulting copolymer maybe tailored to the desired end product and end use.

These aliphatic polyoxaesters described herein and those described inU.S. Pat. Nos. 5,464,929; 5,595,751; 5,597,579; 5,607,687; 5,618,552;5,620,698; 5,645,850; 5,648,088; 5,698,213; and 5,700,583 may be blendedtogether with other homopolymers, copolymers and graft copolymers toimpart new properties to the material formed by the blend. The otherpolymers which the aliphatic polyoxaesters may be blended with includebut are not limited to homopolymer and copolymer of lactone typepolymers with the repeating units described by Formula VIII, aliphaticpolyurethanes, polyether polyurethanes, polyester polyurethanespolyethylene copolymers (such as ethylene-vinyl acetate copolymers andethylene ethyl acrylate copolymers), polyamides, polyvinyl alcohols,poly(ethylene oxide), polypropylene oxide, polyethylene glycol,polypropylene glycol, polytetramethylene oxide, polyvinyl pyrrolidone,polyacrylamide, poly(hydroxy ethyl acrylate), poly(hydroxyethylmethacrylate), absorbable polyoxalates, absorbable polyanhydrides. Thecopolymers (i.e. containing two or more repeating units) includingrandom, block and segmented copolymers. Suitable lactone-derivedrepeating units may be generated from the following monomers include butare not limited to lactone monomers selected from the group consistingof glycolide, d-lactide, 1-lactide, meso-lactide, ε-caprolactone,p-dioxanone, trimethylene carbonate, 1,4-dioxepan-2-one,1,5-dioxepan-2-one and combinations thereof. The blends may containabout 1 weight percent to about 99 weight percent of the aliphaticpolyoxaesters.

For some applications it may be desirable to add additional ingredientssuch as stabilizers, antioxidants radiopacifiers, fillers or the like.

The copolymers and blends of this invention can be melt processed bynumerous methods to prepare a vast array of useful devices. Thesecopolymers and blends can be injection or compression molded to makeimplantable medical and surgical devices, especially wound closuredevices. The preferred wound closure devices are surgical clips, staplesand sutures.

Alternatively, the copolymers and blends can be extruded to preparefibers. The filaments thus produced may be fabricated into sutures orligatures, attached to surgical needles, packaged, and sterilized byknown techniques. The copolymers of the present invention may be spun asmultifilament yarn and woven or knitted to form sponges or gauze, (ornon-woven sheets may be prepared) or used in conjunction with othermolded compressive structures as prosthetic devices within the body of ahuman or animal where it is desirable that the structure have hightensile strength and desirable levels of compliance and/or ductility.Useful embodiments include tubes, including branched tubes, for artery,vein or intestinal repair, nerve splicing, tendon splicing, sheets fortyping up: and supporting damaged surface abrasions, particularly majorabrasions, or areas where the skin and underlying tissues are damaged orsurgically removed.

Additionally, the copolymers and blends can be processed to form films,felts, foams and gels which, when sterilized, are useful as skincoverings or adhesion prevention devices. Another alternative processingtechnique for the copolymer and blends of this invention includessolvent casting, particularly for those applications where a drugdelivery matrix is desired.

In more detail, the surgical and medical uses of the filaments, films,and molded articles of the present invention include, but are notnecessarily limited to:

Knitted products, woven or non-woven, and molded products including:

a. burn dressings

b. hernia patches

c. medicated dressings

d. fascial substitutes

e. gauze, fabric, sheet, felt or sponge for liver hemostasis

f. gauze bandages

g. arterial graft or substitutes

h. bandages for skin surfaces

i. suture knot clip

j. orthopedic pins, clamps, screws, and plates

k. clips (e.g., for vena cava)

l. staples

m. hooks, buttons, and snaps

n. bone substitutes (e.g., mandible prosthesis)

o. intrauterine devices (e.g., spermicidal devices)

p. draining or testing tubes or capillaries

q. surgical instruments

r. vascular implants or supports

s. vertebral discs

t. extracorporeal tubing for kidney and heart-lung machines

u. artificial skin

v. catheters (including, but not limited to, the catheters described inU.S. Pat. No. 4,883,699 which is hereby incorporated by reference)

w. scaffoldings for tissue engineering applications

x. adhesion prevention devices (felts, films, foams and liquids).

In another embodiment, the polyoxaester copolymers (includingprepolymers and suitable crosslinked copolymers and blends) is used tocoat a surface of a surgical article to enhance the lubricity of thecoated surface (or for drug delivery purposes as described hereinafter).The copolymers may be applied as a coating using conventionaltechniques. For example, the copolymers may be solubilized in a dilutesolution of a volatile organic solvent, e.g. acetone, methanol, ethylacetate or toluene, and then the article can be immersed in the solutionto coat its surface. Once the surface is coated, the surgical articlecan be removed from the solution where it can be dried at an elevatedtemperature until the solvent and any residual reactants are removed.

For use in coating applications the copolymers and blends should exhibitan inherent viscosity (initial IV in the case of crosslinkablecopolymers), as measured in a 0.1 gram per deciliter (g/dl) ofhexafluoroisopropanol (HFIP), between about 0.05 to about 2.0 dl/g,preferably about 0.10 to about 0.80 dl/g. If the inherent viscosity wereless than about 0.05 dl/g (final IV for crosslinked copolymers), thenthe copolymer blend may not have the integrity necessary for thepreparation of films or coatings for the surfaces of various surgicaland medical articles. On the other hand, although it is possible to usecopolymer blends with an inherent viscosity greater than about 2.0 dl/g,initial IV for crosslinkable copolymers), it may be exceedinglydifficult to do so.

Although it is contemplated that numerous surgical articles (includingbut not limited to endoscopic instruments) can be coated with thecopolymers and blends of this invention to improve the surfaceproperties of the article, the preferred surgical articles are surgicalsutures and needles. The most preferred surgical article is a suture,most preferably attached to a needle. Preferably, the suture is asynthetic absorbable suture. These sutures are derived, for example,from homopolymers and copolymers of lactone monomers such as glycolide,lactide, ε-caprolactone, 1,4-dioxanone, and trimethylene carbonate. Thepreferred suture is a braided multifilament suture composed ofpolyglycolide or poly(glycolide-co-lactide).

The amount of coating to be applied on the surface of a braided suturecan be readily determined empirically, and will depend on the particularcopolymer or blend and suture chosen. Ideally, the amount of coatingapplied to the surface of the suture may range from about 0.5 to about30 percent of the weight of the coated suture, more preferably fromabout 1.0 to about 20 weight percent, most preferably from 1 to about 5weight percent. If the amount of coating on the suture were greater thanabout 30 weight percent, then it may increase the risk that the coatingmay flake off when the suture is passed through tissue.

Sutures coated with the copolymers and blends of this invention aredesirable because they have a more slippery feel, thus making it easierfor the surgeon to slide a knot down the suture to the site of surgicaltrauma. In addition, the suture is more pliable, and therefore is easierfor the surgeon to manipulate during use. These advantages are exhibitedin comparison to sutures which do not have their surfaces coated withthe copolymers and blends of this invention.

In another embodiment of the present invention when the article is asurgical needle, the amount of coating applied to the surface of thearticle is an amount which creates a layer with a thickness rangingpreferably between about 2 to about 20 microns on the needle, morepreferably about 4 to about 8 microns. If the amount of coating on theneedle were such that the thickness of the coating layer was greaterthan about 20 microns, or if the thickness was less than about 2microns, then the desired performance of the needle as it is passedthrough tissue may not be achieved.

In yet another embodiment of the present invention, the copolymers andblends can be used as a pharmaceutical carrier in a drug deliverymatrix. To form this matrix the copolymers and blends would be mixedwith a therapeutic agent to form the matrix. The variety of differenttherapeutic agents which can be used in conjunction with thepolyoxaesters of the invention is vast. In general, therapeutic agentswhich may be administered via the pharmaceutical compositions of theinvention include, without limitation: antiinfectives such asantibiotics and antiviral agents; analgesics and analgesic combinations;anorexics; antihelmintics; antiarthritics; antiasthmatic agents;anticonvulsants; antidepressants; antidiuretic agents; antidiarrheals;antihistamines; antiinflammatory agents; antimigraine preparations;antinauseants; antineoplastics; antiparkinsonism drugs; antipruritics;antipsychotics; antipyretics, antispasmodics; anticholinergics;sympathomimetics; xanthine derivatives; cardiovascular preparationsincluding calcium channel blockers and beta-blockers such as pindololand antiarrhythmics; antihypertensii,es; diuretics; vasodilatorsincluding general coronary, peripheral and cerebral; central nervoussystem stimulants; cough and cold preparations, including decongestants;hormones such as estradiol and other steroids, includingcorticosteroids; hypnotics; immunosuppressives; muscle relaxants;parasympatholytics; psychostimulants; sedatives; and tranquilizers; andnaturally derived or genetically engineered proteins, polysaccharides,glycoproteins, or lipoproteins.

The drug delivery matrix may be administered in any suitable dosage formsuch as oral, parenteral, a subcutaneously as an implant, vaginally oras a suppository. Matrix formulations containing the copolymers andblends may be formulated by mixing one or more therapeutic agents withthe polyoxaester. The therapeutic agent may be present as a liquid, afinely divided solid, or any other appropriate physical form. Typically,but optionally, the matrix will include one or more additives, e.g.,nontoxic auxiliary substances such as diluents, carriers, excipients,stabilizers or the like. Other suitable additives may be formulated withthe polyoxaester and pharmaceutically active agent or compound, however,if water is to be used it should be added immediately beforeadministration.

The amount of therapeutic agent will be dependent upon the particulardrug employed and medical condition being treated. Typically, the amountof drug represents about 0.001% to about 70%, more typically about0.001% to about 50%, most typically about 0.001% to about 20% by weightof the matrix.

The quantity and type of copolymer blends incorporated into theparenteral will vary depending on the release profile desired and theamount of drug employed. The product may contain blends of copolymershaving different molecular weights to provide the desired releaseprofile or consistency to a given formulation.

The copolymers and blends, upon contact with body fluids including bloodor the like, undergoes gradual degradation (mainly through hydrolysis)with concomitant release of the dispersed drug for a sustained orextended period (as compared to the release from an isotonic salinesolution). This can result in prolonged delivery (over, say 1 to 2,000hours, preferably 2 to 800 hours) of effective amounts (say, 0.0001mg/kg/hour to 10 mg/kg/hour) of the drug. This dosage form can beadministered as is necessary depending on the subject being treated, theseverity of the affliction, the judgment of the prescribing physician,and the like.

Individual formulations of drugs and copolymer or blends may be testedin appropriate in vitro and in vivo models to achieve the desired drugrelease profiles. For example, a drug could be formulated with acopolymer or blend and orally administered to an animal. The drugrelease profile could then be monitored by appropriate means such as, bytaking blood samples at specific times and assaying the samples for drugconcentration. Following this or similar procedures, those skilled inthe art will be able to formulate a variety of formulations.

The copolymers, and blends of the present invention can be crosslinkedto affect mechanical properties. Crosslinking may either be chemicallyor physical. Chemically crosslinked copolymer chains are connected bycovalent bonds, which can be formed by reactive groups contained on thecopolymers, the addition of crosslinking enhancers and/or irradiation(such as gamma-irradiation). Physical crosslinking on the other handconnects the copolymer chains through non-covalent bonds such as van derWaals interactions hydrogen bonding or hydrophobic interactions. Inparticular, crosslinking can be used to control the water swellabilityof said invention.

The polymerizable regions are preferably polymerizable byphotoinitiation by free radical generation, most preferably in thevisible or long wavelength ultraviolet radiation. The preferredpolymerizable regions are acrylates, diacrylates, oligoacrylates,methacrylates, dimethacrylates, oligomethoacrylates, or otherbiologically acceptable photopolymerizable groups.

Other initiation chemistries may be used besides photoinitiation. Theseinclude, for example, water and amine initiation schemes with isocyanateor isothiocyanate containing macromers used as the polymerizableregions.

Useful photoinitiaors are those which can be used to initiate by freeradical generation polymerization of the macromers without cytotoxicityand within a short time frame, minutes at most and most preferablyseconds. Preferred dyes as initiators of choice for long wavelengthultraviolet (LWUV) or visible light initiation are ethyl eosin,2,2-dimethoxy-2-phenyl acetophenone, other acetophenone derivatives, andcamphorquinone. Polymerization and/or crosslinking may be initiatedamong macromers by a light activated free-radical polymerizationinitiator such as 2,2-dimethoxy-2-phenyl acetophenone, otheracetophenone derivatives, and camphorquinone. In other cases,polymerization and/or crosslinking are initiated among macromers by alight-activated free-radical polymerization initiator such as2,2-dimethoxy-2-phenylacetophenone or a combination of ethyl eosin (10-⁴to 10-²M) and triethanol amine (0.001 to 0.1M), for example.

The choice of the photoinitiator is largely dependent on thephotopolymerizable regions. Although we do not wish to be limited byscientific theory, it is believed the macromer includes at least onecarbon—carbon double bond, light absorption by the dye can cause the dyeto assume a triplet state, the triplet state subsequently reacting withthe amine to form a free radical which initiates polymerization.Preferred dyes for use with these materials include eosin dye andinitiators such as 2,2-dimethyl-2-phenylacetophenone,2-methoxy-2-phenylacetophenone, and camphorquinone. Using suchinitiators, copolymers may be polymerized in situ by LWUV light or bylaser light of about 514 nm, for example.

Initiation of polymerization (and in some cases crosslinking) isaccomplished by irradiation with light at a wavelength of between about200-700 nm, most preferably in the long wavelength ultraviolet range orvisible range, 320 nm or higher, most preferably about 514 nm or 365 nm.

There are several photooxidizable and photoreductible dyes that may beused to initiate polymerization. These include acridine dyes, forexample, acriblarine; thiazine dyes, for example, thionine; xanthinedyes, for example, rose bengal; and phenazine dyes, for example,methylene blue. These are used with cocatalysis such as amines, forexample, triethanolamine; sulphur compounds, for example, RSO₂R¹;heterocycles, for example, imidazole; enolates; organometallics; andother compounds, such as N-phenyl glycine. Other initiators includecamphorquinones and acetophenone derivatives.

Thermal polymerization (and optionally crosslinking) initiator systemsmay also be used. Thermal initiators may be selected to allowpolymerization to be initiated at a desired temperature. At times it maybe desired to use a high temperature to initiate polymerization such asduring a molding process. For many medical uses it will be desired touse systems that will initiate free radical polymerization, atphysiological temperatures include, for example, potassium persulfate,with or without tetramethyl ethylenediamine; benzoylperoxide, with orwithout triethanolamine; and ammonium persulfate with sodium bisulfite.

The copolymers (which may be crosslinked) and blends (hereinaftercopolymers) can be used for many of the same uses as describedheretofor. In addition, copolymers can be used for the prevention ofsurgical adhesions, tissue adhesives, tissue coatings (sealants) and intissue engineering.

A preferred application is a method of reducing formation of adhesionsafter a surgical procedure in a patient. The method includes coatingdamaged tissue surfaces in a patient with an aqueous solution of alight-sensitive free-radical polymerization initiator and a macromersolution as described above. The coated tissue surfaces are exposed tolight sufficient to polymerize the macromer. The light-sensitivefree-radical polymerization initiator may be a single compound (e.g.,2,2-dimethoxy-2-phenyl acetophenone) or a combination of a dye and acocatalyst (e.g., ethyl eosin and triethanol amine).

Additionally, the copolymers (which are preferably crosslinked) can alsobe used to form hydrogels that are a three-dimensional network ofhydrophilic polymers in which a large amount of water is present. Ingeneral the amount of water present in a hydrogel is at least 20 weightpercent of the total weight of the dry polymer. The most characteristicproperty of these hydrogels is that it swells in the presence of waterand shrinks in the absence of water. The extent of swelling (equilibriumwater content) is determined by the nature (mainly the hydrophilicity)of the polymer chains and the crosslinking density.

The kinetics of hydrogel swelling is limited by the diffusion of waterthrough the outer layers of the dried hydrogel. Therefore, whilehydrogels swell to a large extent in water, the time it takes to reachequilibrium swelling may be significant depending on the size and shapeof the hydrogel. To reduce the amount of time it takes for a hydrogel toreach equilibrium, hydrogel foams may be used. Hydrogels foams may bemade by crosslinking polymers in the presence of gas bubbles. Thehydrogels foams prepared with macroscopic gas cells will have an opencelled structure similar to sponges except that the pore size willgenerally be an order of magnitude larger.

Hydrogels may be used for many of same uses that have been described forpolyoxaesters such as wound dressings materials, since the crosslinkedhydrogels are durable, non-antigenic, and permeable to water vapor andmetabolites, while securely covering the wound to prevent bacterialinfection. Hydrogels may also be used for coatings in general andmedical coatings in particular. The hydrogel coatings may provide asmooth slippery surface and prevent bacterial colonization on thesurface of the medical instrument. For example hydrogels may be used ascoatings on urinary catheter surfaces to improve its biocompatability.Hydrogels may also be used in a variety of applications where themechanical swelling of the hydrogel is useful such as in catheters as ablend component with a biocompatable elastomer (such as the elastomerdescribed in U.S. Pat. No. 5,468,253 hereby incorporated by reference).Additionally, hydrogels could be used for drug delivery orimmobilization of enzyme substrates or cell encapsulization. Other usesfor hydrogels have been described in the literature, many of which arediscussed in chapter one of Hydrogels and Biodegradable Polymers forBioapplications, published by the Amercian Chemical Society (which ishereby incorporated by reference herein).

Crosslinking to form crosslinked structures can be performed in a.variety of ways. For example the polymers may be crosslinked while beingsynthesized, such as by utilizing multifunctional monomers or oligomers.However, crosslinking at other times is also advantageous. For examplecrosslinking may be performed during the manufacture of a device such byadding a thermal initiator to the copolymer prior to injection molding adevice. Additionally, crosslinking of a polymerizable region with aphotoinitiator may be performed during stereolithography to formdevices. European Patent Application 93305586.5 describes the processfor performing stereolithography (with photopolymerizable materials). Aspreviously discussed photoinitiation may be used in vivo to crosslinkthe copolymers of the present invention for various wound treatmentssuch as adhesion prevention and wound sealing. Coating may also beapplied to devices and crosslinked in situ to form films that willconform to the surface of the device.

In a further embodiment of the present invention the polyoxaesters andpolymer blends of the present invention can be used in tissueengineering applications as supports for cells. Appropriate tissuescaffolding structures are known in the art such as the prostheticarticular cartilage described in U.S. Pat. No. 5,306,311, the porousbiodegradable scaffolding described in WO 94/25079, and theprevascularized implants described in WO 93/08850 (all herebyincorporated by reference herein). Methods of seeding and/or culturingcells in tissue scaffoldings are also known in the art such as thosemethods disclosed in EPO 422 209 B1, WO 88/03785, WO 90/12604 and WO95/33821 (all hereby incorporated by reference herein).

The Examples set forth below are for illustration purposes only, and arenot intended to limit the scope of the claimed invention in any way.Numerous additional embodiments within the scope and spirit of theinvention will become readily apparent to those skilled in the art.

EXAMPLE 1 Preparation of 3,6-Dioxaoctanedioic Acid Dimethylester

The diacid, 3,6-dioxaoctanedioic acid, was synthesized by oxidation oftriethylene glycol. The oxidation was carried out in a 500 milliliter,three-neck round bottom flask equipped with a thermometer, an additionalfunnel, a gas absorption tube and a magnetic spinbar. The reaction flaskwas lowered into an oil bath resting upon a magnetic stirrer. To thereaction flask was added 157.3 ml of a 60% nitric acid solution; 37.0 gof triethylene glycol was added to the additional funnel. The contentsof the flask were heated to 78-80° C. A test tube containing 0.5 g ofglycol and one milliliter of concentrated nitric acid was warmed in awater bath until brown fumes started appearing. The contents were thenadded to the reaction flask. The mixture was stirred for a few minutes;the glycol was then carefully added. The rate of addition had to bemonitored extremely carefully to keep the reaction under control. Theaddition rate was slow enough so that the temperature of the exothermicreaction mixture was maintained at 78-82° C. After the addition wascompleted (80 minutes), the temperature of the reaction mixture wasmaintained at 78-80° C. for an additional hour. While continuing tomaintain this temperature range, the excess nitric acid and water wasthen distilled off under reduced pressure (water suction). The syrupyresidue was cooled; some solids appeared. The reaction product had theIR and NMR spectra expected for the dicarboxylic acid; the crude productwas used as such for esterification.

Esterification of the crude 3,6-dioxaoctanedioic acid was accomplishedas follows: To the reaction flask containing 36 g of the crude diacid,was added 110 ml of methanol. This was stirred for 3 days at roomtemperature after which 15 g of sodium bicarbonate was added and stirredovernight. The mixture was filtered to remove solids. To the liquor wasadded an additional 10 g of sodium bicarbonate; this mixture was stirredovernight. The mixture was again filtered; the liquor was fractionallydistilled.

NMR analysis of the esterified product showed a mixture of dimethyltriglycolate (78.4 mole %) and monomethyltriglycolate (21.6 mole %). Nosignificant condensation of diacid was observed.

EXAMPLE 2 Preparation of Polyoxaester from the Methyl Esters of3,6-Dioxaoctanedioic Acid and Ethylene Glycol

A flame dried, mechanically stirred, 50-milliliter glass reactorsuitable for polycondensation reaction, was charged with 20.62 g(approximately 0.1 mole) of the methyl esters of 3,6-dioxaoctanedioicacid from Example 1, 18.62 g (0.3 mole) of distilled ethylene glycol,and 0.0606 ml of a solution of 0.33M stannous octoate in toluene. Afterpurging the reactor and venting with nitrogen, the temperature wasgradually raised over the course of 26 hours to 180° C. A temperature of180° C. was then maintained for another 20 hours; all during theseheating periods under nitrogen at one atmosphere, the methanol formedwas collected. The reaction flask was allowed to cool to roomtemperature; it was then slowly heated under reduced pressure (0.015-1.0mm) over the course of about 32 hours to 160° C., during which timeadditional distillates were collected. A temperature of 160° C. wasmaintained for 4 hours after which a sample, a few grams in size, of thepolymer formed was taken. The sample was found to have an inherentviscosity (I.V.) of 0.28 dl/g, as determined in hexaflouroisopropanol(HFIP) at 25° C. at a concentration of 0.1 g/dl. The polymerization wascontinued under reduced pressure while raising the temperature, in thecourse of about 16 hours, from 160° C. to 180° C.; a temperature of 180°C. was maintained at for an additional 8 hours, at which time a polymersample was taken and found to have an I.V. of 0.34 dl/g. The reactionwas continued under reduced pressure for another 8 hours at 180° C. Theresulting polymer has an inherent viscosity of 0.40 dl/g, as determinedin HFIP at 25° C. and at a concentration of 0.1 g/dl.

EXAMPLE 3 Preparation of Polyoxaester with 3,6,9-TrioxaundecanedioicAcid and Ethylene Glycol

A flame dried, mechanically stirred, 250-milliliter glass reactor,suitable for polycondensation reaction, was charged with 44.44 g (0.2mole) of 3,6,9-trioxaundecanedioic acid, 62.07 g (1.0 mole) of distilledethylene glycol, and 9.96 milligrams of dibutyltin oxide. After purgingthe reactor and venting with nitrogen, the contents of the reactionflask were gradually heated under nitrogen at one atmosphere, in thecourse of about 32

hours, to 180° C., during which time the water formed was collected. Thereaction mass was allowed to cool to room temperature. The reaction masswas then heated under reduced pressure (0.015-1.0 mm), graduallyincreasing the temperature to 180° C. in about 40 hours; during thistime additional distillates were collected. The polymerization wascontinued under reduced pressure while maintaining 180° C. for anadditional 16 hours. The resulting polymer has an inherent viscosity of0.63 dl/g as determined in HFIP at 25° C. and at a concentration of 0.1g/dl.

EXAMPLE 4 Preparation of Polyoxaester with Polyglycol Diacid andEthylene Glycol

A flame dried, mechanically stirred, 500-milliliter glass reactor(suitable for polycondensation reaction) was charged with 123.8 g (0.2mole) polyglycol diacid (molecular weight about 619), 62.07 g (1.0 mole)of distilled ethylene glycol, and 9.96 milligrams of dibutyltin oxide.After purging the reactor and venting with nitrogen, the contents of thereaction flask was heated under nitrogen at one atmosphere, graduallyincreasing the temperature to 200° C. in about 32 hours; during thistime the water formed was collected. The reaction flask was heatedgradually under reduced pressure (0.015-1.0 mm) from room temperature to140° C. in about 24 hours, during which time additional distillates werecollected. A polymer sample of about ten grams was taken at this stage,and found to have an I.V. of 0.14 dl/g in HFIP at 25° C., 0.1 g/dl. Thepolymerization was continued under reduced pressure while heating from140° C. to 180° C. in about 8 hours, and then maintained at 180° C. foran additional 8 hours. A polymer sample was again taken and found tohave an I.V. of 0.17 dl/g. The reaction temperature was then increasedto 190° C. and maintained there under reduced pressure for an additional8 hours. The resulting polymer has an inherent viscosity of 0.70 dl/g asdetermined in HFIP at 25° C. and at a concentration of 0.1 g/dl.

EXAMPLE 5 Copolymer of Polyoxaester/Caprolactone/Trimethylene Carbonateat 5/5/5 by Weight

A flame dried, 50-milliliter, round bottom single-neck flask was chargedwith 5 grams of the aliquot of the polyoxaester of Example 4 having anI.V. of 0.14 dl/g, 5.0 grams (0.0438 mole) of ε-caprolactone, 5.0 grams(0.0490 mole) of trimethylene carbonate, and 0.0094 milliliters of a0.33 molar solution of stannous octoate in toluene.

The flask was fitted with a magnetic stirrer bar. The reactor was purgedwith nitrogen three times before venting with nitrogen. The reactionmixture was heated to 160° C. and maintained at this temperature forabout 6 hours. The copolymer was dried under vacuum (0.1 mm Hg) at 80°C. for about 16 hours to remove any unreacted monomer. The copolymer hasan inherent viscosity of 0.34 dl/g, as determined in HFIP at 25° C. andat a concentration of 0.1 g/dl. The copolymer is a viscous liquid atroom temperature. The mole ratio of polyoxaester/PCL/PTMC was found byNMR analysis to be 47.83/23.73/28.45.

EXAMPLE 6 Copolymer of Polyoxaester/Caprolactone/Glycolide at 6/8.1/0.9by Weight

A flame dried, 25-milliliter, round bottom, single-neck flask wascharged with 6 grams of the polyoxaester of Example 4 having an I.V. of0.17 dl/g., 8.1 grams (0.0731 mole) of ε-caprolactone, 0.9 grams (0.008)mole of glycolide and 0.0080 milliliters of a 0.33 molar stannousoctoate solution in toluene. The flask was fitted with a magneticstirrer bar. The reactor was purged with nitrogen three times beforeventing with nitrogen. The reaction mixture was heated to 160° C. andmaintained at this temperature for about 18 hours. The copolymer has aninherent viscosity of 0.26 dl/g in HFIP at 25° C. and at a concentrationof 0.1 g/dl. The copolymer is solid at room temperature. The mole ratioof polyoxaester/PCL/PGA/caprolactone was found by NMR analysis to be56.54/37.73/3.79/1.94.

EXAMPLE 7 In Vitro Hydrolysis

The polyoxaester of Example 3 was tested for in vitro hydrolysis at both50° C. and at reflux temperature. A 100 mg sample of the polyoxaester,placed in 100 ml of a phosphate buffer solution (0.2 M in phosphate, pH7.27), was completely hydrolyzed in about 7 days at 50° C., whereas atreflux it was completely hydrolyzed in about 16 hours.

EXAMPLE 8 In Vitro Hydrolysis

Polyoxaester of Example 2 was tested for in vitro hydrolysis at 50° C.and at reflux temperature. A 100 mg sample of the polyoxaester, placedin a 100 ml buffer solution (pH 7.27), was completely hydrolyzed inabout 25 days at 50° C., whereas at reflux it was completely hydrolyzedin about 16 hours.

EXAMPLE 9 Preparation of Polyoxaester Based on Polyglycol Diacid withPolyethylene Glycol

To a flame-dried, 250-ml, 2-neck flask suitable for polycondensationreaction, 15.13 grams of polyglycol diacid (m.w. 619g/m; 0.02444 mole),15.0 grams polyethylene glycol (m.w. 600g/m; Aldrich, 0.025 mole), 3.18grams ethylene glycol (m.w. 62.07g/m, 0.0512 mole were charged, anddried over night under high vacuum at room temperature. The next day,2.5 mg of dibutyl tin oxide (m.w. 248.92) was added. The reaction mass,under nitrogen at one atmosphere, was then gradually heated to 200° C.over a period of 16 hours while collecting the distillate. The reactionflask was allowed to cool to room temperature and the pressure reduced.Now under vacuum, it was gradually heated to 180-200° C., and run atthis temperature until the desired molecular weight was obtained. Theresulting copolymer has an I.V. of 0.63 dl/g.

EXAMPLE 10 Preparation of Polyoxaester Hydrogel Based on PolyglycolDiacid with Polyethylene Glycol

To a flame-dried, 250 ml, 2 neck flask, suitable for polycondensationreaction, 77.34 grams of polyglycol diacid (m.w. 619; 0.125 mole), 63.60grams of polyethylene glycol (m.w. 600; Aldrich, 0.106 mole), 15.52grams of ethylene glycol (m.w. 62.07; 0.250 mole), and 2.55 grams oftrimethylol propane (m.w. 134.18; 0.019 mole) were charged and driedover night under high vacuum at room temperature. The next day, 12.5 mgof dibutyl tin oxide (m.w 248.92) was charged. The reaction mass, undernitrogen at one atmosphere, was then gradually heated to 190-200° C.over a period of 16 hours while collecting the distillate. The reactionflask was allowed to cool to room temperature and the pressure reduced.Now under vacuum, it was gradually heated to 170° C. and maintainedthere about 22 hours. The resulting viscous polymer was transferred intoa tray for devolatalized in a vacuum oven until a film formed. Theresulting film was light brown in color. It swelled in water and wasfound to disappeared in about two weeks.

EXAMPLE 11 Preparation of Copolymers of Polyoxaester Based on Adipic andPolyglycol Diacids with Polyethylene Glycol

The following is an example of how a copolymer of polyoxaester could beprepared. To a flame-driedi 250-ml, 2-neck flask suitable forpolycondensation reaction, 15.13 grams of polyglycol diacid (m.w.619g/m; 0.02444 mole), 0.893 grams of adipic acid (m.w. 146.14 g/m;0.00611 mole), 15.0 grams polyethylene glycol (m.w. 600 g/m; Aldrich,0.025 mole), 3.18 grams ethylene glycol (m.w. 62.07g/m, 0.0512 mole canbe charged, and dried over night under high vacuum at room temperature.The next day, a suitable catalyst at a suitable level (i.e. 2.5 mg ofdibutyl tin oxide) can be added. The reaction mass, under nitrogen atone atmosphere, can then be gradually heated to 200° C. over a period of16 hours while collecting the distillate. The reaction flask can beallowed to cool to room temperature and the pressure reduced. Now undervacuum, it can be gradually heated to elevated temperatures (i.e.180-200° C. or higher) and kept at elevated temperatures until thedesired molecular weight is obtained. The ester moieties of theresultant copolymer are approximately 20% adipate in nature. Althoughthe initial charge is rich, on a mole basis, in ethylene glycol, thediol based moieties in the resultant copolymer are much richer inpolyethylene glycol-based moieties due to differences in relativevolatility.

We claim:
 1. A device containing a polyoxaester copolymer formed from afirst divalent repeating unit of formula IA: [—O—C(O)—R₃₀—C(O)—]  IA asecond divalent repeating unit of the formula IB:[O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IB and a third repeatingunit selected from the group of formulas consisting of:[—O—R₄—]_(A),  II [—O—R₅—C(O)—]_(B),  III ([—O—R₅—C(O)]_(P)—O—)_(L)G  XIand combinations thereof, wherein R₃₀ is an alkylene, arylene,arylalkylene, substituted alkylene, substituted arylene and substitutedalkylarylene provided that R₃₀ cannot be—[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; R₁, R′₁, R₂ and R′₂ areindependently hydrogen or an alkyl group containing 1 to 8 carbon atoms;R₃ is an alkylene unit containing from 2 to 12 carbon atoms or is atoxyalkylene group of the following formula:—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IV wherein C is an integer in the rangeof from 2 to about 5, D is an integer in the range of from about 0 toabout 2,000, and E is an integer in the range of from about 2 to about5,except when D is zero, in which case E will be an integer from 2 to12; R₄ is an alkylene unit containing from 2 to 8 carbon atoms; A is aninteger in thy range of from 1 to 2,000; R₅ is selected from the groupconsisting of —C(R₆)(R₇)—, —(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—,—(CH₂)₅—, —(CH₂)_(F)—O—C(O)— and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ areindependently hydrogen or an alkyl containing from 1 to 8 carbon atoms;R₈ is hydrogen or methyl; F is an integer in the range of from 2 to 6; Bis an integer in the range of from 1 to n such that the number averagemolecular weight of formula III is less than about 200,000; P is aninteger in the range of from 1 to m such that the number averagemolecular weight of formula XI is less than about 1,000,000; Grepresents the residue minus from 1 to L hydrogen atoms from thehydroxyl groups of an alcohol previously containing from 1 to about 200hydroxyl groups; and L is an integer from about 1 to about
 200. 2. Thedevice of claim 1 wherein the device is a surgical device.
 3. The deviceof claim 1 wherein the absorbable surgical device is selected from thegroup consisting of burn dressings, hernia patches, medicated dressings,fascial substitutes, gauze, fabrics, sheets, felts, sponges, gauzebandages, arterial graft, bandages for skin surfaces, suture knot clips,pins, clamps, screws, plates, clips, staples, hooks, buttons, snaps,bone substitutes, intrauterine devices, tubes, surgical instruments,vascular implants, vascular supports, vertebral discs, and artificialskin.
 4. The device of claim 1 wherein the device is a filament.
 5. Thedevice of claim 4 wherein the filament is attached to a needle.
 6. Thedevice of claim 1 wherein the device contains a polyoxaester copolymerthat has been crosslinked.
 7. A coated device having a coatingcontaining a polyoxaester copolymer formed from a first divalentrepeating unit of formula A: [—O—C(O)—R₃₀—C(O)—]  IA a second divalentrepeating unit of the formula IB:[O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IB and a third repeatingunit selected from the group of formulas consisting of:[—O—R₄—]_(A),  II (—O—R₅—C(O)—]_(B),  III ([—O—R₅—C(O)]_(P)—O—)_(L)G  XIand combinations thereof, wherein R₃₀ is an alkylene, arylene,arylalkylene, substituted alkylene, substituted arylene and substitutedalkylarylene provided that R₃₀ cannot be—[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; R₁, R′₁, R₂ and R′₂ areindependently hydrogen or an alkyl group containing 1 to 8 carbon atoms;R₃ is an alkylene unit containing from 2 to 12 carbon atoms or is anoxyalkylene group of the following formula:—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IV wherein C is an integer in the rangeof from 2 to about 5, D is an integer in the range of from about 0 toabout 2,000, and E is an integer in the range of from about 2 to about5, except when D is zero, in which case E will be an integer from 2 to12; R₄ is an alkylene unit containing from 2 to 8 carbon atoms; A is aninteger in the range of from 1 to 2,000; R₅ is selected from the groupconsisting of —C(R₆)(R₇)—, —(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—,—(CH₂)₅—, —(CH₂)_(F)—O—C(O)— and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ areindependently hydrogen or an alkyl containing from 1 to 8 carbon atoms;R₈ is hydrogen or methyl; F is an integer in the range of from 2 to 6; Bis an integer in the range of from 1 to n such that the number averagemolecular weight of formula III is less than about 200,000; P is aninteger in the range of from 1 to m such that the number averagemolecular weight of formula XI is less than about 1,000,000; Grepresents the residue minus from 1 to L hydrogen atoms from thehydroxyl groups of an alcohol previously containing from 1 to about 200hydroxyl groups; and L is an integer from about 1 to about
 200. 8. Thecoated device of claim 7 wherein the device is a suture.
 9. The coateddevice of claim 7 wherein the device is a needle.
 10. A drug deliverymatrix comprising a drug and a polyoxaester copolymer formed a firstdivalent repeating unit of formula I: [—O—C(O)—R₃₀—C(O)—]  IA a seconddivalent repeating unit of the formula IB:[O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IB and a third repeatingunit selected from the group of formulas consisting of:[—O—R₄—]_(A),  II [—O—R₅—C(O)—]_(B),  III ([—O—R₅—C(O)]_(P)—O—)_(L)G  XIand combinations thereof, wherein R₃₀ is an alkylene, arylene,arylalkylene, substituted alkylene, substituted arylene and substitutedalkylarylene provided that R₃₀ cannot be—[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; R₁, R′₁, R₂ and R′₂ areindependently hydrogen or an alkyl group containing 1 to 8 carbon atoms;R₃ is an alkylene unit containing from 2 to 12 carbon atoms or is aoxyalkylene group of the following formula:—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)  IV wherein C is an integer in the rangeof from 2 to about 5, D is an integer in the range of from about 0 toabout 2,000, and E is an integer in the range of from about 2 to about5, except when D is zero, in which case E will be an integer from 2 to12; R₄ is an alkylene unit containing from 2 to 8 carbon atoms; A is aninteger in the range of from 1 to 2,000; R₅; is selected from the groupconsisting of —C(R₆)(R₇)—, —(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—,—(CH₂)₅—, —(CH₂)_(F)—O—C(O)— and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ areindependently hydrogen or an alkyl containing from 1 to 8 carbon atoms;R₈ is hydrogen or methyl; F is an integer in the range of from 2 to 6; Bis an integer in the range of from 1 to n such that the number averagemolecular weight of formula III is less than about 200,000; P is aninteger in the range of from 1 to m such that the number averagemolecular weight of formula XI is less than about 1,000,000; Grepresents the residue minus from 1 to L hydrogen atoms from thehydroxyl groups of an alcohol previously containing from 1 to about 200hydroxyl groups; and L is an integer from about 1 to about
 200. 11. Thedevice of claim 1 wherein the number average molecular weight of formulaXI in the polyoxaester copolymer is less than 200,000.
 12. The device ofclaim 1 wherein the polyoxaester copolymer has the formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—O)_(S′)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)(C(O)—R₅—O)_(B)]_(W)  XIIwherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the range of from about 1 to about 1,000.
 13. The device ofclaim 1 wherein the polyoxaester copolymer has the formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—O)_(S′)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)([—O—R₅—C(O)]_(P)—O—)_(L)G]_(W)  XIIIwherein R₄ and R′₄ a e independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000 S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the range of from about 1 to about 1,000.
 14. The coateddevice of claim 7 wherein the polyoxaester copolymer has the formula:[O—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—]_(N′)[—O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—]_(N)wherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; N and N′ are independent integersin the range of from about 1 to about 10,000.
 15. The coated device ofclaim 7 wherein the polyoxaester copolymer has the formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)′_(A)—O)′_(S)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)(C(O)—R₅—O)_(B)]_(W)  XIIwherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the range of from about 1 to about 1,000.
 16. The coateddevice of claim 7 wherein the polyoxaester copolymer has the formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)′_(A)—O)′_(S)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)([—O—R₅—C(O)]_(P)—O—)_(L)G]_(W)  XIIIwherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the range of from about 1 to about 1,000.
 17. The drugdelivery matrix of claim 10 wherein the polyoxaester copolymer has theformula:[O—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—]_(N′)[—O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—]_(N)wherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; N and N′ are independent integersin the range of from about 1 to about 10,000.
 18. The drug deliverymatrix of claim 10 wherein the number average weight of formula XI ofthe polyoxaester copolymer is less than 200,000.
 19. The drug deliverymatrix of claim 10 wherein the polyoxaester copolymer has he formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—O)_(S′)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)([—O—R₅—C(O)]_(P)—O—)_(L)G]_(W)  XIIIwherein R₄ and R′₄ are independelntly selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integerin the range of from 1 to about 2,000; S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the rang of from about 1 to about 1,000.
 20. The polyoxaestercopolymer of claim 1 wherein the polyoxaester copolymer contains as athird repeat unit a lactone derived repeating unit derived from lactonemonomers selected from the group consisting of glycolide, d-lactide,1-lactide, meso-lactide, ε-caprolactone, p-dioxanone, trimethylenecarbonate, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and combinationsthereof.
 21. The device of claim 1 wherein the polyoxaester copolymercontains as a third repeat unit a lactone derived repeating unit derivedfrom lactone monomers selected from the group consisting of glycolide,d-lactide, 1-lactide, meso-lactide, ε-caprolactone, p-dioxanone,trimethylene carbonate, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one andcombinations thereof.
 22. The device coated of claim 2 wherein thepolyoxaester copolymer in the coating contains as a third repeat unit alactone derived repeating unit derived from lactone monomers selectedfrom the group consisting of glycolide, d-lactide, 1-lactide,meso-lactide, ε-caprolactone, p-dioxanone, trimethylene carbonate,1,4-dioxepan-2-one, 1,5-dioxepan-2-one and combinations thereof.
 23. Thedrug delivery matrix of claim 10 wherein the polyoxaester copolymer inthe matrix contains as a third repeat unit a lactone derived repeatingunit derived from lactone monomers selected from the group consisting ofglycolide, d-lactide, 1-lactide, meso-lactide, ε-caprolactone,p-dioxanone, trimethylene carbonate, 1,4-dioxepan-2-one,1,5-dioxepan-2-one and combinations thereof.
 24. A polymer blendcomprising a polyoxaester copolymer formed from a first divalentrepeating unit of formula IA: [—O—C(O)—R₃₀—C(O)—]  IA a second divalentrepeating unit of the formula IB:[O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IB and a third repeatingunit selected from the group of formulas consisting of:[—O—R₄ ]_(A),  II [—O—R₅—C(O)—]_(B),  III ([—O—R₅—C(O)]_(P)—O—)_(L)G  XIand combinations thereof, wherein R₃₀ is an alkylene, arylene,arylalkylene, substituted alkylene, substituted arylene and substitutedalkylarylene provided that R₃₀ cannot be —[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; R₁, R′₁, R₂ and R′₂ are independentlyhydrogen or an alkyl group containing 1 to 8 carbon atoms; R₃ is analkylene unit containing from 2 to 12 carbon atoms or is an oxyalkylenegroup of the following formula: —[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IVwherein C is an integer in the range of from 2 to about 5, D is aninteger in the range of from about 0 to about 2,000, and E is an integerin the range of from about 2 to about 5, except when D is zero, in whichcase E will be an integer from 2 to 12; R is an alkylene unit containingfrom 2 to 8 carbon atoms; A is an integer in the range of from 1 to2,000; R₅ is selected from the group consisting of —C(R₆)(R₇)—,—(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—, —(CH₂)₅—, —(CH₂)_(F)—O—C(O)—and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ are independently hydrogen or analkyl containing from 1 to 8 carbon atoms; R₈ is hydrogen or methyl; Fis an integer in the range of from 2 to 6; B is an integer in the rangeof from 1 to n such that the number average molecular weight of formulaIII is less than about 200,000; P is an integer in the range of from 1to m such that the number average molecular weight of formula XI is lessthan about 1,000,000; G represents the residue minus from 1 to Lhydrogen atoms from the hydroxyl groups of an alcohol previouslycontaining from 1 to about 200 hydroxyl groups; and L is an integer fromabout 1 to about 200; and a second polymer selected from the groupconsisting of homopolymer and copolymer of lactone type polymers withthe repeating units described by formulas III and XI, aliphaticpolyurethanes, polyether polyurethanes, polyester polyurethanes,polyethylene copolymers, polyamides, polyvinyl alcohols, poly(ethyleneoxide), polypropylene oxide, polyethylene glycol, polypropylene glycol,polytetramethylene oxide, polyvinyl pyrrolidone, polyacrylamide,poly(hydroxy ethyl acrylate), poly(hydroxyethyl methacrylate),absorbable polyoxalates, absorbable polyanhydrides and combinationsthereof.
 25. The polymer blend of claim 24 wherein the polyoxaestercopolymer has the formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—O)_(S′)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)(C(O)—R₅—O)_(B)]_(W)  XIIwherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the range of from about 1 to about 1,000.
 26. The polymerblend of claim 24 wherein the polyoxaester copolymer has the formula:[(—C(O)—R₃₀—C(O)—(O—R′₄)_(A′)—O)_(S′)(—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—(O—R₄)_(A)—O)_(S)([—O—R₅—C(O)]_(P)—O—)_(L)G]_(W)  XIIIwherein R₄ and R′₄ are independently selected from alkylene groupscontaining from 2 to 8 carbon atoms; A and A′ are independently integersin the range of from 1 to about 2,000; S and S′ are independentlyintegers in the range of from about 1 to about 10,000 and W is aninteger in the range of from about 1 to about 1,000.
 27. A device ofclaim 1 wherein the device additionally contains blended with thepolyoxaester copolymer a second polymer selected from the groupconsisting of homopolymer and copolymer of lactone type polymers withthe repeating units described by formulas III and XI, aliphaticpolyurethanes, polyether polyurethanes, polyester polyurethanes,polyethylene copolymers, polyamides, polyvinyl alcohols, poly(ethyleneoxide), polypropylene oxide, polyethylene glycol, polypropylene glycol,polytetramethylene oxide, polyvinyl pyrrolidone, polyacrylamide,poly(hydroxy ethyl acrylate), poly(hydroxyethyl methacrylate) absorbablepolyoxalates, absorbable polyanhydrides and combinations thereof. 28.The device of claim 27 wherein the device is a surgical device.
 29. Thedevice of claim 28 wherein the surgical device is selected from thegroup consisting of burn dressings, hernia patches, medicated dressings,fascial substitutes, gauze, fabrics, sheets, felts, sponges, gauzebandages, arterial graft, bandages for skin surfaces, suture knot clip,pins, clamps, screws, plates, clips, staples, hooks, buttons, snaps,bone substitutes, intrauterine devices, tubes, surgical instruments,vascular implants, vascular supports, vertebral discs, and a artificialskin.
 30. The device of claim 28 herein the device is a catheter. 31.The device of claim 30 wherein the catheter contains an elastomericcopolymer.
 32. The device of claim 31 wherein the elastomeric polymer isa copolymer of ε-caprolactone and glycolide.
 33. A coated device ofclaim 7 wherein coating additionally contains a second polymer selectedfrom the group consisting of homopolymer and copolymer of lactone typepolymers with the repeating units described by formulas III and XI,aliphatic polyurethanes, polyether polyurethanes, polyesterpolyurethanes, polyethylene copolymers, polyamides, polyvinyl alcohols,poly(ethylene oxide), polypropylene oxide, polyethylene glycol,polypropylene glycol, polytetramethylene oxide, polyvinyl pyrrolidone,polyacrylamide, poly(hydroxy ethyl acrylate), poly(hydroxyethylmethacrylate) absorbable polyoxalates, absorbable polyanhydrides andcombinations thereof.
 34. The drug delivery matrix of claim 10 whereinthe matrix additionally contains a second polymer selected from thegroup consisting of homopolymer and copolymer of lactone type polymerswith the repeating units described by formulas III and XI, aliphaticpolyurethanes, polyether polyurethanes, polyester polyurethanes,polyethylene copolymers, polyamides;, polyvinyl alcohols, poly(ethyleneoxide), polypropylene oxide, polyethylene glycol, polypropylene glycol,polytetramethylene oxide, polyvinyl pyrrolidone, polyacrylamide,poly(hydroxy ethyl acrylate), poly(hydroxyethyl methacrylate) absorbablepolyoxalates, absorbable polyanhydrides and combinations thereof. 35.The polymer blend of claim 24 wherein the polyoxaester copolymercontains as a third repeat unit a lactone derived repeating unit derivedfrom lactone monomers selected from the group consisting of glycolide,d-lactide, 1-lactide, meso-lactide, ε-caprolactone, p-dioxanone,trimethylene carbonate, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one andcombinations thereof.
 36. The device of claim 27 wherein thepolyoxaester copolymer contains as a third repeat unit a lactone derivedrepeating unit derived from lactone monomers selected from the groupconsisting of glycolide, d-lactide, 1-lactide, meso-lactide,ε-caprolactone, p-dioxanone, trimethylene carbonate, 1,4-dioxepan-2-one,1,5-dioxepan-2-one and combinations thereof.
 37. The coated device ofclaim 33 wherein the polyoxaester copolymer in the coating contains as athird repeat unit a lactone derived repeating unit derived from lactonemonomers selected from the group consisting of glycolide, d-lactide,1-lactide meso-lactide, ε-caprolactone, p-dioxanone, trimethylenecarbonate, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and combinationsthereof.
 38. The drug delivery matrix of claim 34 wherein thepolyoxaester copolymer in the matrix contains as a third repeat unit alactone derived repeating unit derived from lactone monomers selectedfrom the group consisting of glycolide, d-lactide, 1-lactide,meso-lactide, ε-caprolactone, p-dioxanone, trimethylene carbonate,1,4-dioxepan-2-one, 1,5-dioxepan-2-one and combinations thereof.
 39. Thecoated device of claim 7 wherein the device that is coated is a stent.40. The device of claim 1 wherein the device is an adhesion preventiondevice.
 41. The device of claim 1 wherein the polyoxaester copolymer iscontacted with water to form a hydrogel.
 42. A polyoxaester copolymerformed from a polyoxaester copolymer having a first divalent repeatingunit of formula IA: [—O—C(O)—R₃₀—C(O)—]  IA a second divalent repeatingunit of the formula IB: [O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IBand a third repeating unit selected from the group of formulasconsisting of: [—O—R₄—]A,  II [—O—R₅—C(O)—]_(B),  III([—O—R₅—C(O)]_(P)—O—)_(L)G  XI, wherein R₃₀ is an alkylene, arylene,arylalkylene, substituted alkylene, substituted arylene and substitutedalkylarylene provided that R₃₀ cannot be—[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; R₁, R′₁, R₂ and R′₂ areindependently hydrogen or an alkyl group containing 1 to 8 carbon atoms;R₃ is an alkylene unit containing from 2 to 12 carbon atoms or is anoxyalkylene group of the following formula:—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IV wherein C is an integer in the rangeof from 2 to about 5, D is an integer in the range of from about 0 toabout 2,000, and E is an integer in the range of from about 2 to about5, except when D is zero, in which case E will be an integer from 2 to12; R₄ is an alkylene unit containing from 2 to 8 carbon atoms; A is aninteger in the range of from 1 to 2,000, R₅ is selected from the groupconsisting of —C(R₆)(R₇)—, —(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—,—(CH₂)₅—, —(CH₂)F—O—C(O)— and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ areindependently hydrogen or an alkyl containing from 1 to 8 carbon atoms;R₈ is hydrogen or methyl; F is an integer in the range of from 2 to 6; Bis an integer in the range of from 1 to n such that the number averagemolecular weight of formula III is less than about 200,000; P is aninteger in the range of from 1 to m such that the number averagemolecular weight of formula XI is less than about 1,000,000; Grepresents the residue minus from 1 to L hydrogen atoms from thehydroxyl groups of an alcohol previously containing from 1 to about 200hydroxyl groups; and L is an integer from about 1 to about 200, whereinthe polyoxaester copolymer is linked to one or more polymerizableregions.
 43. The polyoxaester copolymer of claim 42 wherein thepolyoxaester copolymer has been crosslinked.
 44. The polyoxaestercopolymer of claim 43 wherein the polyoxaester copolymer has beencrosslinked by the addition of a coupling agent.
 45. A polyoxaestercopolymer formed from a polyoxaester copolymer having a first divalentrepeating unit of formula IA: [—O—C(O)—R₃₀—C(O)—]  IA a second divalentrepeating unit of the formula IB:[O—C(O)—C(R₁)(R₂)—O—R₃—O—C(R′₁)(R′₂)—C(O)—]  IB and a third repeatingunit selected from the group of formulas consisting of: [—O—R₄—]A,  II[—O—R₅—C(O)—]_(B),  III ([—O—R₅—C(O)]_(P)—O—)_(L)G  XI, wherein R₃₀ isan alkylene, arylene, arylalkylene, substituted alkylene, substitutedarylene and substituted alkylarylene provided that R₃₀ cannot be—[C(R₁)(R₂)]₁₋₂—O—(R₃)—O—[C(R′₁)(R′₂)]₁₋₂—; R₁, R′₁, R₂ and R′₂ areindependently hydrogen or an alkyl group containing 1 to 8 carbon atoms;R₃ is an alkylene unit containing from 2 to 12 carbon atoms or is anoxyalkylene group of the following formula:—[(CH₂)_(C)—O—]_(D)—(CH₂)_(E)—  IV wherein C is an integer in the rangeof from 2 to about 5, D is an integer in the range of from about 0 toabout 2,000, and E is an integer in the range of from about 2 to about5, except when D is zero, in which case E will be an integer from 2 to12; R₄ is an alkylene unit containing from 2 to 8 carbon atoms; A is aninteger in the range of from 1 to 2,000; R₅ is selected from the groupconsisting of —C(R₆)(R₇)—, —(CH₂)₃—O—, —CH₂—CH₂—O—CH₂—, —CR₈H—CH₂—,—(CH₂)₅—, —(CH₂)_(F)—O—C(O)— and —(CH₂)_(F)—C(O)—CH₂—; R₆ and R₇ areindependently hydrogen or an alkyl containing from 1 to 8 carbon atoms;R₈ is hydrogen or methyl; F is an integer in the range of from 2 to 6; Bis an integer in the range of from 1 to n such that the number averagemolecular weight of formula III is less than about 200,000; P is aninteger in the range of from 1 to m such that the number averagemolecular weight of formula XI is less than about 1,000,000; Grepresents the residue minus from 1 to L hydrogen atoms from thehydroxyl groups of an alcohol previously containing from 1 to about 200hydroxyl groups; and L is an integer from about 1 to about 200, whereinthe crosslinked polyoxaester copolymer has been contacted with water toform a hydrogel.